The proposed project involves the synthesis of phenolic derivatives of colchicine for pharmacological evaluation and for the synthesis of prodrugs useful in the treatment of cancer. Chemical methods of O-demethylation as well as microbiological systems known to carry out this type reaction will be investigated to prepare such derivatives. These products will be evaluated for their antitumor and tubulin-polymerization inhibiting activities. Prodrug derivatives will be examined in vitro and in vivo for hydrolysis, antineoplastic activity, and routes of metabolism in mammals. The interaction of colchicine with model sulflhydryl compounds will also be undertaken to aid in elucidating the mechanism of action of colchicine in inhibiting tubulin polymerization and as an antitumor agent.